Oral ingestion is the most common method of drug administration. Oral ingestion is the safest, the most convenient and the most economical form of drug administration. Furthermore, because oral ingestion comprises administering dosage forms such as tablets and capsules that are relatively small, and because drug absorption often is rapidly completed, drug absorption is limited usually to the stomach and to the small intestine. The small intestine is the primary site from which orally administered drugs are absorbed, and few drugs are absorbed in any significant dose from the stomach.
There are several biological reasons for the small intestine serving as the primary site for drug absorption. For example, the small intestine has an absorptive area about two-hundred times greater than the absorptive area of the stomach for increasing the dose of drug absorbed per unit time. In addition, the intestinal epithelium is more permeable to the passage of drug than is the mucosal lining of the stomach permeable to the passage of drug, thereby increasing the absorptive ability of the intestine. Moreover, the quantity of blood flow through the intestinal capillaries is greater than in the stomach, which leads to more drug being admitted into the systemic circulation from the intestine. Generally, the intestine is designed from drug absorption, while the stomach can be considered a reservoir where drug is released in increments to the small intestine for absorption therein. The drug absorption properties of the stomach and the intestine are presented in the following references: The Pharmacological Basis of Therapeutics, by Goodman and Gilman, 8th Ed., pages 6 and 7, (1990); Drug Interactions Newsletter, by Hansten and Horn, Vol. 9, pages 475 to 480, (1989); and, Novel Drug Delivery And Its Therapeutic Application, by Prescott and Nimmo, Ch. 8, pages 79 to 88, and Ch. 9, pages 89 to 101, (1989).
The prior art administered drugs orally using non-controlled dosage forms that delivered a drug throughout the entire gastrointestinal tract consisting of the stomach, small intestine, large intestine and the rectal vault. While the prior art possessed the ability to deliver a drug throughout the entire gastrointestinal tract, the prior art lacked the precision required for delivering a drug only to the stomach and only to the primary site of absorption, the small intestine. The prior art delivered drug from the stomach to the rectal vault results in the administration of unneeded drug, which can be accompanied often by unwanted side effects.
It is self evident from the above presentation to those versed in the dispensing drug art to which this invention pertains that a pressing need exits for a rate controlled dosage form that can deliver a valuable drug to a preselected absorption site of the gastrointestinal tract. This pressing need exists for an oral dosage form that can deliver a drug to the preferred sites of absorption at a controlled rate in a constant dose per unit time over a selected period of time. The need exists for such a dosage form that delivers a drug for its therapeutic effect substantially independent of the variable environment of the gastrointestinal tract. It will be appreciated further by those versed in the dispensing art, that such a novel and unique dosage form that can administer a drug to a preselected area of the gastrointestinal tract in a rate controlled dose over time, and simultaneously provide for the desired site-specific therapy, such a dosage form would represent an advancement and a valuable contribution to the drug delivery art.